The photoreceptors in the eye are responsible for vision. There are two types of photoreceptors: rods and cones. Rods are responsible for vision in low level light and they have little to do with color vision. Cones function in bright light and are vital for color vision. Vision loss occurs when the photoreceptors aren’t working. Recent research has revealed that the function of photoreceptors is more intricate than previously believed. Moreover, research done on dogs has opened to the way to adapting the findings for humans.
Studies conducted at the University of California Los Angeles (UCLA) have demonstrated that dormant photoreceptors aren’t exactly dormant. While mutations in the rod photoreceptor leads to their death and prompts retinal degeneration, the cone photoreceptors don’t die. In fact, they remain alive and viable.
Previous research suggested that the cones in this situation were dormant and not functional. Work done by Alapakkam Sampath, the Grace and Walter Lantz Endowed Chair in Ophthalmology at the UCLA Jules Stein Eye Institute and professor at the David Geffen School of Medicine at the university reveal that signals recorded from a mouse retina demonstrate that the processing of visual information isn’t as compromised as expected and that treatments can one day be developed to protect the cones so that vision can be preserved.
Furthermore, downstream signals from the retina, particularly from the ganglion cells, show less drop off than expected. The reason for this might be attributed to inner retina mechanisms that are working to minimize the sensitivity difference to preserve signaling in the ganglion cells. These findings are consistence with what is known about the brain. Homeostatic mechanisms, which the brain most definitely is, respond to injury and disease by covering up the deficiency. That is the reason why neurological problems are hard to detect until they become severe.
What about an eye disease like, retinitis pigmentosa, which affects over 100,000 people in the U.S. alone? What has research learned in this area? Namely, that a treatment that works for dogs is being developed for humans. Work done in the lab of Simon Petersen-Jones, professor and Donald R. Myers and William E. Dunlap Endowed Chair in Canine Health at Michigan State University’s College of Veterinary Medicine led to gene therapy for dogs that have the CNGB1 retinitis pigmentosa. Since it worked so well in dogs, this treatment is being modified for use in humans.
The therapy works by way of an adeno-associated virus vector to deliver a normal copy of the CNGB1 gene that is controlled by a novel gene promoter. The novel promoter is a modified form of the promoter human rhodopsin, which is an important gene found in retinal rod cells. This promoter ensures that the CNGB1 gene that is being delivered is active in the target cell, specifically the rod photoreceptor.
This treatment works by introducing a normal working copy of the CNGB1 gene. The introduction of this gene rescues the normal function of the rod cells and restores the rod-mediated vision. It also stops the toxic amounts of the cyclic guanosine monophosphate in normally functioning rods. If the cyclic guanosine monophosphate is not controlled, it causes cell death. In addition, the treatment preserves cone function and retinal structure by stopping photoreceptor degeneration.
Recent research at UCLA has revealed the working of photoreceptors and uncovered the surprising viability of what were thought to be dormant cones. This work highlights what could be future treatments that would protect vision by maintaining cone function. In addition, insights from canine retinitis pigmentosa studies at Michigan State University, show that adapting therapies that work in dogs can benefit humans. These studies demonstrate the advances made in understanding ocular mechanisms and show promise for the development of treatments that could change the eye disease management landscape.
Sources:
https://www.brainfacts.org/thinking-sensing-and-behaving/vision/2018/rods-and-cones-061518
https://askabiologist.asu.edu/rods-and-cones
https://www.uclahealth.org/news/conesvisualfunction
https://msutoday.msu.edu/news/2023/dog-eye-therapy-human-clinical-trial